Field of the Invention
The invention generally relates to methods for the diagnosis and treatment of neurological and neurodegenerative diseases, disorders, and associated processes.
Background Information
Alzheimer's Disease (AD) is the most common cause of dementia and is an increasing public health problem. It is currently estimated to afflict 5 million people in the United States, with an expected increase to 13 million by the year 2050 (Herbert et al, 2001, Alzheimer Dis. Assoc. Disord. 15(4): 169-173). AD, like other central nervous system (CNS) degenerative diseases, is characterized by disturbances in protein production, accumulation, and clearance. In AD, dysregulation in the metabolism of the protein, amyloid-beta (Aβ), is indicated by a massive buildup of this protein in the brains of those with the disease. AD leads to loss of memory, cognitive function, and ultimately independence and death. The disease takes a heavy personal and financial toll on the patient, the family, and society. Because of the severity and increasing prevalence of this disease in the population, it is urgent that better treatments be developed.
Currently, there are some medications that modify symptoms, however, there are no disease-modifying treatments. Disease-modifying treatments will likely be most effective when given before the onset of irreversible brain damage. However, by the time clinical diagnosis of AD is made, extensive neuronal loss has already occurred (Price et al. 2001, Arch. Neurol. 58(9): 1395-1402). Therefore, a way to identify those at risk of developing AD would be most helpful in preventing or delaying the onset of AD. Currently, there are no means of identifying the pathophysiologic changes that occur in AD before the onset of clinical symptoms or of effectively measuring the effects of treatments that may prevent the onset or slow the progression of the disease.
A need therefore exists for a sensitive, accurate, and reproducible method for quantifying biomolecules in a subject. Previous technologies used for absolute quantitation include enzyme linked immunosorbent assays (ELISAs), which use antibodies to capture and measure the concentrations. However, ELISAs quantitate total concentration or rely on isoform specific antibodies for quantitation and can, for the most part, be used to measure the concentration of only one species per assay. Antibodies are highly specific for the protein species and the conformations of the proteins they bind and the reliance upon two antibodies binding to the protein of interest can lead to high inter- and intra-assay variability in the reported concentrations from ELISA assays. As such, a method is needed for measuring the absolute quantitation of the concentrations of one or more biomolecules in biological fluids and tissues in vivo, where the biomolecules are associated with the diagnosis and/or progression of diseases.